Is Long-Term Anti-TNF Therapy Efficacious in Pediatric IBD?

Children with inflammatory bowel diseases may experience anti-TNF failure within the first 5 years of treatment.

A large proportion of pediatric patients with inflammatory bowel disease (IBD) initiated on anti-TNF agents experience long-term treatment failure, according to study findings in Digestive and Liver Disease.

With the rise in pediatric IBD incidence, including Crohn disease (CD) and ulcerative colitis (UC), it becomes increasingly important to assess the safety of treatment options. Researchers conducted a retrospective cohort study to assess the long-term efficacy of anti-TNF agents in treating pediatric IBD.

The researchers sourced data from the French EPIMAD registry, which includes health information from 6 million patients in Northern France. The study was part of a project focused on the impact of therapeutic strategies on the natural history of pediatric IBD (INSPIRED). 

Outcomes included primary nonresponse, loss of response, and intolerance. Primary nonresponse was defined as anti-TNF withdrawal with active disease and/or intestinal resection within 3 months of treatment initiation. Loss of response was defined as anti-TNF withdrawal with active disease after initial response and at least 3 months after treatment initiation. 

[O]ur present results suggest that anti-TNF have similar treatment persistence rates when used as first- or second-line treatments.

All patients with a diagnosis of CD and UC were screened for analysis. Of 1,007 patients with CD and 337 patients with UC, 481 (47.7%) patients with CD and 81 (24.0%) with UC received at least 1 anti-TNF agent.

Of the 481 patients with CD on anti-TNF agents, there were 397 (82.5%) patients treated with infliximab, 83 (17.3%) with adalimumab, and 1 (0.2%) with certolizumab. Results show that the probable failure rate at years 1, 3, and 5 was similar between infliximab (30.7% [95% CI, 25.7-35.3]; 51.3% [95% CI, 45.2-56.8]; and 61.9% [95% CI, 55.1-67.7]) and adalimumab (25.9% [95% CI, 14.4-35.9]; 49.3% [95% CI, 33.5-61.3]; and 57.7% [95% CI, 38.3-71.0]; P = .740). 

Primary failure or loss of response accounted for 25.5% (95% CI, 21.0-30.1) and 19.4% (95% CI, 9.9-29.0) of the infliximab and adalimumab groups in CD, respectively. 

Of the 81 patients with UC treated with anti-TNF therapy, 71 (87.7%) received infliximab, 10 (12.3%) received adalimumab, and 5 (6.2%) patients received combination therapy.

The probability of failure at years 1, 3, and 5 were 38.4% [95% CI, 25.2-49.3], 52.3% [95% CI, 36.6-64.2], and 72.7% [95% CI, 42.3-87.1] for infliximab and 12.5% [95% CI, 0.0-32.7], 12.5% [95% CI, 0.0-32.7] and 12.5% [95% CI, 0.0-32.7] for adalimumab (P = .091). 

Primary failure or loss of response accounted for 29.3% [95% CI, 18.2-40.5], 36.0% [95% CI, 23.6-48.4], and 47.3% [95% CI, 29.4-65.1] at 1, 3, and 5 years, respectively, for patients with UC treated with infliximab. 

In patients with CD, female gender was the only factor significantly associated with anti-TNF failure (HR, 1.62; 95% CI, 1.23-2.12). There were no patient factors associated with treatment failure in UC.

Study limitations include a small sample size of patients requiring second-line anti-TNF treatment and the unavailability of systematic endoscopic and biomarkers assessment or therapeutic drug monitoring. 

“Interestingly, our present results suggest that anti-TNF have similar treatment persistence rates when used as first- or second-line treatments,” the study authors noted. 

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Fumery M, Dupont C, Ley D, et al. Long-term effectiveness and safety of anti-TNF in pediatric-onset inflammatory bowel diseases: a population-based study. Dig Liver Dis. Published online May 1, 2023. doi:10.1016/j.dld.2023.04.017